Multi-target regulation of pro-inflammatory cytokine production by transcription factor Blimp-1.
Multi-target regulation of pro-inflammatory cytokine production by transcription factor Blimp-1.
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转录因子 Blimp™1 对促炎症细胞因子产生的多靶点调节
DOI：
10.1007/s00011-022-01671-2
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发表时间：
2023-03
期刊：
影响因子：
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细胞因子风暴综合征是一种与传染性和自身免疫性疾病相关的致命疾病。本研究旨在探讨Blimp-1对多种细胞因子产生的调控机制。将Blimp1 shRNA转染RAW264.7巨噬细胞，然后进行toll样受体（TLR）配体刺激。采用实时荧光定量PCR和流式细胞仪检测细胞因子mRNA和蛋白水平。免疫荧光染色检测AP-1和NF-κB p65的核易位。用5 × NF-κB报告子或il - 6启动子报告子荧光素酶检测转录活性。在多种TLR配体刺激下，Blimp-1显著抑制巨噬细胞IL-1β、IL-6和IL-18的表达和分泌。免疫荧光染色结果显示，Blimp-1严格控制lps攻击巨噬细胞NF-κB p65的核易位。此外，Blimp-1直接抑制NF-κB的转录活性和IL6基因的转录。Blimp-1通过直接结合基因组区域，限制NF-κB的核易位和转录活性，抑制多种促炎细胞因子的产生。这一发现可能为细胞因子风暴相关疾病提供潜在的治疗策略。在线版本包含补充材料，下载地址为10.1007/s00011-022-01671-2。
Cytokine storm syndrome is a fatal condition related to infectious and autoimmune diseases. Here, we aim to investigate the regulatory mechanisms of Blimp-1 on multiple cytokine production. The Blimp1 shRNA was transfected into RAW264.7 macrophages, followed by Toll-like receptor (TLR) ligand stimulation. The mRNA and protein levels of cytokines were detected by real-time PCR and flow cytometric bead array. The nuclear translocation of AP-1 and NF-κB p65 was measured by immunofluorescence staining. The transcriptional activity was detected by luciferase reporter assay with 5 × NF-κB reporter or with IL6 promoter reporter. Blimp-1 significantly inhibited the expression and secretion of IL-1β, IL-6, and IL-18 in macrophages during stimulation with a variety of TLR ligands. The immunofluorescence staining results showed that Blimp-1 strictly controlled the nuclear translocation of NF-κB p65 in LPS-challenged macrophages. Furthermore, Blimp-1 directly inhibited the transcriptional activity of NF-κB and the transcription of IL6 gene. Blimp-1 represses the production of multiple pro-inflammatory cytokines by directly binding the genomic region and restricting the nuclear translocation and transcriptional activity of NF-κB. This finding may provide potential therapeutic strategies for the cytokine storm-related diseases. The online version contains supplementary material available at 10.1007/s00011-022-01671-2.
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影响因子：
7.3
作者：
Nadeau S;Martins GA
通讯作者：
Martins GA
DOI：
10.1084/jem.20110658
发表时间：
2011-10-24
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Kim SJ;Zou YR;Goldstein J;Reizis B;Diamond B
通讯作者：
Diamond B
影响因子：
5.3
作者：
Saha, Gundappa;Khamar, Bakulesh M.;Dubey, Vikash Kumar
通讯作者：
Dubey, Vikash Kumar
转录因子 Blimp-1 在健康和疾病中对单核吞噬细胞的调节。
影响因子：
6.4
作者：
Ulmert I;Henriques-Oliveira L;Pereira CF;Lahl K
通讯作者：
Lahl K
影响因子：
30.5
作者：
通讯作者：
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